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Endometriosis is an enigmatic disease that affects approximately 10-15% of women of reproductive age. There are no incidence figures, but prevalence is said to be increasing along with an earlier age at diagnosis. A growing body of evidence supports an etiologic relation between hormonally active environmental chemicals and endometriosis. This is based on a significant dose-dependent increase in incidence and severity of endometriosis in dioxin-exposed Rhesus monkeys and an ability to spontaneously and surgically induce disease in exposed rodents. Five preliminary human studies focusing on dioxin and polychlorinated biphenyl exposure have produced results suggesting a relation in women, while one failed to find an effect. Our recently completed study piloting a methodology for investigating this question at the population level confirmed a significant relation between total PCBs and organochlorine pesticides and risk of endometriosis. Specifically, risk of endometriosis increased 150% with higher total serum concentrations of anti-estrogenic environmental agents. [This will be the first study to report this effect.] Given the small sample size, we were unable to analyze serum concentrations by severity of disease or to consider confounders, such as dietary estrogens, other hormonal exposures, body fat, or reproductive history.
We propose a definitive study to answer the question whether exposure to polyhalogenated aromatic hydrocarbon chemicals, a class of persistent ubiquitous environmental chemicals capable of bio-accumulating and bio-magnifying within the food chain, is associated with incidence and severity of endometriosis in women. This question cannot be answered with clinical populations given the potential for differences in exposure profiles between those who do or do not seek care, as well as changes in body burdens over childbirth and lactation. To achieve our goal, a case control study design is proposed. Cases will comprise women undergoing incident laparoscopy/laparotomy in whom endometriosis is visually confirmed and staged consistent with gynecologic practices (n=425). Two control groups are needed given that visual inspection of the pelvis is a requirement for establishing the presence/absence of disease. The first comprises women undergoing laparoscopy for sterilization procedures and in whom no endometriosis is diagnosed (n=425). The second group will comprise women aged 18-44 years with no self-report of endometriosis, infertility or history of laparoscopy/laparotomy, randomly selected from the referent population (n=187). This ensures a population-based approach and an opportunity to address the methodologic challenges facing study of endometriosis outside selective clinical populations and ensuing biases.
All participants will be given a baseline interview and asked to provide a blood specimen for toxicological analysis. For cases and controls undergoing laparoscopy/laparotomy, visceral fat also will be collected. This will ensure accurate measurement of the chemical exposures since these compounds are lipophilic. A subsample of women from the case and control groups will be asked to undergo a diagnostic MRI to assess the reliability of disease status based upon visual inspection of the pelvis. We will thus have an opportunity to objectively measure visceral fat, compared with subcutaneous deposits. Our study is sufficiently powered for hypothesis testing while enabling us to develop methodologies for modeling of exposure and disease.
This study is directly responsive to NICHD’s Mission while addressing racial disparity including that arising from environmental injustice.
